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Secondary debulking surgery improved overall survival (OS) for select women with recurrent ovarian cancer in first relapse, an updated analysis from the DESKTOP III trial showed, representing the first phase III trial to demonstrate a survival benefit with such an approach.

Among over 400 patients meeting prespecified criteria, secondary cytoreductive surgery prior to second-line chemotherapy extended median OS from 46 to 53.7 months (HR 0.75, 95% CI 0.58-0.96, P=0.02), though the benefit was reserved for the group that achieved a complete resection, reported Andreas du Bois, MD, PhD, of the German Gynecological Oncology Group (AGO) at the American Society of Clinical Oncology (ASCO) virtual meeting.

In the phase III SOC-1 trial from China, also presented at the meeting, secondary debulking surgery in a slightly younger population improved median progression-free survival (PFS) at first relapse versus chemotherapy alone (17.4 vs 11.9 months, HR 0.58, 95% CI 0.45-0.74, P<0.001), but not among those with residual disease following surgery, according to Rongyu Zang, MD, PhD, of Zhejiang Cancer Hospital in Hangzhou.

Findings from the two trials arrive on the heels of GOG-213, which suggested that second cytoreductive surgery might do more harm than good in recurrent ovarian cancer, albeit in a less stringently selected group of women.

"Both investigators tout that use of a triage algorithm to select patients for surgery can lead to complete gross resection rate in nearly three-quarters of patients," said ASCO discussant and GOG-213 investigator Robert Coleman, MD, of U.S. Oncology Research in Woodlands, Texas. "However, the price paid for being wrong is substantial, with no benefit seen in progression-free survival, and possibly a detriment in overall survival."

Addressing the disparate findings, Coleman pointed out that in GOG-213, surgical decision-making was left to the discretion of investigators, with guidance that tumors be amenable to complete gross resection based on imaging and clinical factors. But the trial saw a slightly lower complete resection rate (67%) compared to the two new studies (about 75%).

"Criteria for patient selection is probably best represented by one of the validated algorithms," said Coleman. "Surgery in this setting is remarkably consistent."

But more notable, he said, was the over-performance of the control arm in GOG-213 due to widespread use (84%) of bevacizumab (Avastin), which was associated with improved outcomes. "Concomitant maintenance bevacizumab outperformed arms where it was not used," he said.

DESKTOP III

From 2010 to 2014, DESKTOP III randomized 407 women with recurrent ovarian cancer in first relapse to chemotherapy alone or surgery followed by chemotherapy at 80 centers across 12 countries -- a platinum-containing regimen was strongly recommended and used in 90% of cases. To be eligible for the trial, all women were required to meet AGO criteria for surgery, which was developed and prospectively validated in the DESKTOP I/II trials, and consists of good performance status (ECOG 0), complete resection at initial cytoreductive surgery, and ascites <500 mL.

Patients in the current study were also required to have had a platinum-free interval of at least 6 months, though in most (74%) this exceeded a year (median 19.9 months).

"DESKTOP III is the first prospectively randomized trial showing an overall survival benefit of debulking surgery in recurrent ovarian cancer," du Bois said during his presentation. "The overall survival benefit was highest, and exclusively seen in the cohort with complete resection, indicating the importance of thorough selection of both the right patient and the right center."

OS in the complete resection group reached a median of 61.9 months, as compared to 28.8 months for those with residual disease following surgery (HR 0.40, 95% CI 0.28-0.59, P<0.001).

To translate the results into daily practice, du Bois suggested that women with a positive AGO score who meet other trial eligibility be counseled and given the option of secondary surgery at a specialized and experienced center.

"Remember, 50% of patients with a platinum-free interval of more than 6 months will have a positive score, and 75% of them will end up with a complete resection of all visible disease," he said. "The median survival gain in this group of patients is almost 16 months if they receive a complete resection, and this is worth going for."

Of the 206 women assigned to the surgery arm, 187 (91%) ultimately underwent their operation. Consistent with an interim analysis of DESKTOP III, surgery also improved PFS by more than 4 months, from 14.0 months with chemotherapy alone to 18.4 months with the combined approach (HR 0.66, 95% CI 0.54-0.82, P<0.001).

Baseline characteristics were well balanced, with a median patient age of 62 in the chemotherapy-only arm and 61 in the surgery arm. About three-fourths had International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IV disease, and more than 80% had grade 2/3 histology. PARP inhibitor use was rare (<5%), and about one-fourth of the cohort received bevacizumab.

There were no deaths within 30 days in the surgery group, and one within 90 days. In the control arm, 11% later went on to have cytoreductive surgery.

SOC-1

From 2012 to 2019, SOC-1 randomized 356 women with recurrent ovarian cancer in first relapse to secondary cytoreductive surgery plus chemotherapy or chemotherapy alone. The trial used different eligibility criteria than DESKTOP III. While patients also needed to have had a platinum-free interval of at least 6 months, an iMODEL score ≤4.7 was used, and two investigators had to agree that complete resection was possible based on imaging. With this criteria, more than three-fourths were able to achieve a complete resection (76.7%).

Patients without remaining disease following surgery had a median PFS of 19.1 months, while those with residual disease had similar outcomes to the chemotherapy-alone arm (12.6 vs 11.9 months, respectively, HR 1.10, 95% CI 0.74-1.63), Zang reported.

Median OS data were immature, but favored the surgery arm over the no-surgery arm (58.1 vs 53.9 months, HR 0.82, 95% CI 0.57-1.19). The 3-year OS rate was 68% versus 66%, respectively. For those with residual disease, OS was worse with chemotherapy alone, at 34.8 months.

Women in the study had a median age of 54, and over 80% had FIGO stage III/IV disease and serous tumors. Median platinum-free interval in the cohort prior to study entry was 16.1 months. In the surgery arm, no deaths occurred within 90 days. In the control arm, more than a third of women later went on to surgery at subsequent recurrences of their disease.